复方丹参制剂不同配伍对丹酚酸B在大鼠血浆中药代动力学参数的影响

Effect of different combinations of compound Danshen preparation on pharmacokinetic parameters of salvianolic acid B in rat plasma

目的：建立检测大鼠血浆中丹酚酸B分析方法，并探讨复方丹参制剂不同配伍给药后对丹酚酸B的影响。方法：分别采用复方丹参制剂（双参通冠方）不同配伍方式灌胃给药，溶剂沉淀法提取含药血浆中的酚酸类成分，采用LC—MS—MS方法测定血药浓度，DAS软件对结果进行统计分析。结果：色谱采用Agilent SB—C18反相柱，流动相乙腈-甲醇-0．1％甲酸梯度洗脱，质谱采用MRM方式进行检测，丹酚酸B的线性范围为0．5—1000μg·L^-1，R^2=0．999，最低检测限为0．5μg·L^-1，提取回收率为30．88％～38．18％，方法的精密度、准确度和稳定性均符合要求。结论：本方法操作简单、专属性强、灵敏度高、准确性好。药代动力学研究发现与单一丹参组分给药相比，配伍应用均可使丹酚酸B的AUC降低，表观分布容积和清除率增加。

Objective： A sensitive liquid chromatography-mass spectrometric （LC-MS） method for the quantification of salvianolic acid B in rat plasma was developed and validated. The effect of different combination on the salvianolic acid B were studied to investigate SSTG＇pharmacokinetics mechanism. Method： Different combination methods were used for oral administration. The compounds were extracted by solvent in rat plasma and determined using LC-MS-MS method. The results were analysis by DAS software. Result： Chromatographic separation was achieved on a reversed-phase SB-C18 column with the mobile phase of acetonitrile-methanolformic acid （0. 1% ） and step gradient elution resulted. The analytes were detected by using an electrospray negative ionization mass spectrometry in the MRM mode. The method showed excellent linearity over the concentration range 0. 5-1 000 μg · L^-1 （R2 = 0. 999）. The low limit of quantification was 0. 5 μg · L^-1 The extract recoveries of analytes were from 30. 88% to 38. 18%. The pre- cisions, the accuracy and the stability all meet the requirements for all analytes. The HPLC-MS-MS technique provided an excellent method for the quantification of SAB in rat plasma. Conclusion： The method is simple, sensitive and rapid. The plasma concentration of Rg1 and Re were too low to determine. Ginseng ＆ Yanhusuo and Ginseng ＆ Danshen combination can decrease the AUC value and increase the Vd and CI.